The freeway continues northeasterly towards Trenton, where it interchanges with I-195 and Route 29 before bypassing the city to the east, north, and west, crossing the Delaware River on the Scudder Falls Bridge into Pennsylvania.

From this junction, the highway heads southeast on an eight-lane freeway maintained by the Delaware Department of Transportation that passes to the northeast of suburban neighborhoods in Wilmington Manor.

The road has an eastbound ramp to Landers Lane before it passes between residential neighborhoods and comes to a cloverleaf interchange with DE 9 north of the city of New Castle.

The highway runs through a mix of farmland and woodland and enters Oldmans Township, where it comes to an interchange providing access to Straughns Mill Road (CR 643).

[2][8] I-295 crosses the Oldmans Creek into Logan Township in Gloucester County and passes near some residential development and Pureland Industrial Complex as it comes to the Center Square Road (CR 620) exit.

Continuing northeast, the freeway passes over Conrail Shared Assets Operations' Penns Grove Secondary railroad line and reaches an interchange with Route 44 and Delaware Street (CR 640).

Route 44 ends at a cul-de-sac that has a ramp from the southbound direction of I-295/US 130 prior to another exit that provides access to Red Bank Avenue (CR 644).

Past this, I-295 continues east as a six-lane freeway through wooded areas near suburban development, passing under Conrail Shared Assets Operations' Grenloch Industrial Track line before reaching an interchange with Black Horse Pike (Route 168).

The highway heads east along the border between Haddon Heights to the north and Barrington to the south and passes over Conrail Shared Assets Operations' Beesleys Point Secondary railroad line before reaching the interchange with White Horse Pike (US 30) near its intersection of Clements Bridge Road/Highland Avenue (Route 41/CR 573).

After this, I-295 curves northeast and passes through a corner of Tavistock before entering a part of Haddonfield and coming to a trumpet interchange providing access to Woodcrest Station along the PATCO Speedline.

The highway crosses into Cherry Hill and passes over the tracks carrying the PATCO Speedline and NJ Transit's Atlantic City Line before it reaches the Haddonfield-Berlin Road (CR 561) exit.

The roadway runs through wooded areas with suburban neighborhoods to the west and the New Jersey Turnpike to the east as it comes to a cloverleaf interchange at Route 70.

[2][8] I-295 enters Mount Laurel in Burlington County upon crossing Pennsauken Creek and runs northeast through woods near development, reaching a cloverleaf interchange with Route 73 that provides access to the New Jersey Turnpike to the east.

Past this, the road passes east-northeast near commercial areas to the southeast of Moorestown Mall before curving northeast to closely follow the turnpike.

Past this, the road curves north and reaches the exit for US 130 west of Bordentown before passing through woodland and crossing over NJ Transit's River Line.

[2][8] I-295 crosses the Crosswicks Creek into Hamilton in Mercer County and runs through woods and marshland a short distance east of the Delaware River.

A scenic overlook of the river is located along the southbound side of the road; access from the northbound lanes is provided by a pedestrian bridge over the highway.

It reaches the interchange with Route 31 and passes through Ewing before returning to Hopewell Township, crossing under CSX Transportation's Trenton Subdivision railroad line.

[14] At this point, maintenance of the road changes from the New Jersey Department of Transportation to the Delaware River Joint Toll Bridge Commission, and I-295 widens from six to eight lanes.

After crossing the Delaware Canal, I-295 reaches an interchange with Taylorsville Road, which provides indirect access to PA 32, to the north of Yardley, and narrows to six lanes.

Immediately after this interchange, I-295 passes over Norfolk Southern Railway's Morrisville Line and CSX Transportation's Fairless Branch as it curves southwest, heading northwest of commercial development and the Oxford Valley Mall.

Following this interchange, the freeway crosses the Mill Creek and runs south-southeast near suburban residential areas as it heads west of Levittown.

[7][8] In the 1927 New Jersey state highway renumbering, Route 39 was legislated to begin at the Yardley–Wilburtha Bridge and bypass Trenton to the north and east before continuing south to Hammonton along present-day US 206.

[17][18] Portions of I-295 in Salem and Gloucester counties predate the Interstate Highway System as part of freeway bypasses for the surface section of US 130/Route 44 through Carneys Point and between Bridgeport and Westville.

The section of the present highway between the New Jersey Turnpike and the present-day CR 618 bridge was built as part of the US 130 bypass of Carneys Point in 1953.

[5] The concurrent Route 44 designation was removed from US 130 in the 1953 New Jersey state highway renumbering[17][18] and was later assigned to the former surface alignment of US 130 through Carneys Point and between Bridgeport and Westville.

To bridge the gap, motorists from northbound I-95 were directed to follow I-295 southbound and I-195 eastbound to reach the New Jersey Turnpike to continue north along I-95, and vice versa.

In 2003, the rest areas along I-295 in Burlington County were closed as part of funding cuts in Governor Jim McGreevey's budget, saving the state $1 million a year.

The Pennsylvania Department of Transportation finished Phase 3 in July of the same year, signing their section as east–west despite its north–south alignment to avoid a change in direction from north to south on the same route.

[48] The structurally deficient Scudder Falls Bridge, that carried I-295 over the Delaware River between Lower Makefield Township, Pennsylvania, and Ewing, New Jersey, was in need of a replacement.